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Immunodeficiency is a physiologic state in which the immune system succumbs to microbiologic exposures typically controlled by members of the nonimmunodeficient population. This state can be transient or persistent, in-born or acquired, and it can result from dysfunction of one or multiple components of the immune system. The infectious manifestations of immunodeficiency arise from a failure to prevent, clear, limit the spread, or suppress a microorganism that would typically be controlled in one of the modes of defense. Clinical manifestations therefore include infection with an unusual microorganism, greater extent of spread of an infection, persistent infection, recurrent infection, and the associated inflammatory consequences of these scenarios. Since infections in immunodeficiency are dependent on a relevant microbiologic exposure, it is possible that immunodeficiency can remain undiagnosed; however, careful consideration of associated features, family history, immunosuppressive medications, and laboratory findings can hasten the diagnosis and possibly prevent a severe infection or other complication. As a result, it is important that physicians be aware of clues that could lead to a prompt diagnosis.

The human immune system consists of the phylogenetically more primitive innate immune system and the adaptive immune system (Figure 33–1). For the purpose of clinical categorization, primary immunodeficiencies (PIDs) are commonly divided into four main groups: antibody deficiencies, combined T- and B-cell immunodeficiencies, phagocyte disorders, and other deficiencies of the innate immunity, which include complement deficiencies. Understanding the role each part of the immune system plays in host defense allows critical evaluation for possible immunodeficiency as the cause of recurrent infections and immune dysregulation, which can lead to associated autoimmunity and chronic inflammation.

Figure 33–1.

Components of the human immune system.


When evaluating for a possible PID, other conditions that increase susceptibility to infections must be considered, such as allergic rhinitis, asthma, cystic fibrosis, primary ciliary dyskinesia, foreign-body aspiration, and conditions that interfere with skin barrier function. Common causes of secondary or acquired immunodeficiency such as malnutrition; aging; protein loss via gastroenteropathy, kidney disease, or lymphatic malformations; certain drugs (glucocorticoids, immunosuppressive medications, disease-modifying biologic drugs, chemotherapy); and other diseases associated with impaired immunity (bone marrow failure and blood cell malignancies, and certain chronic infections, including AIDS). If a single site is involved, anatomic defects and foreign bodies may be present. Figure 33–2 outlines when PIDs should be considered.

Figure 33–2.

General approach to primary immunodeficiencies.

Key clinical patterns can indicate the presence of a PID and the category of immune impairment. PID should be considered in patients with frequent, severe, or unusual infections. When the infection history suggests PID, the type of infections can help guide the initial workup. Antibody, complement, and phagocyte defects predispose mainly to bacterial infections, but diarrhea, superficial candidiasis, opportunistic infections, ...

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